Afatinib

Detailed information

General information about assessment reports

Since 2006, an Environmental Risk Assessment (ERA) for the active pharmaceutical substance shall accompany an application for a marketing authorisation in EU for a medicinal product for human use. Parts of environmental data can be found in the public investigation report (PAR/EPAR for medicinal product through a centralized procedure). Since the benefit/risk assessment for human medicinal products at present does not include environmental effects, an update of the environmental risk assessment is not required for renewals of marketing authorizations. There is thus no requirement for companies to stay informed about the development of their substances from an environmental point of view and consequently to update the environmental risk assessment as new data are published.

Assessment report

Assessment report for Giotrif (afatinib), 25 July 2013, EMA/491185/2013.

Hazard

Persistence: OECD 308:
"DT_{50, water} =0.8, day/river; 1.1 day/pond
DT_{50, sediment} =dissipation half-lives, not reached
DT_{50, whole system} =6.8, days/river; 2.3 days/pond, % shifting to sediment = 48.1%/river; 62.5%/pond (at day 99)."

Bioaccumulation: log D (pH 7.4) = 3.8
BCF fisk 9.2–9.7.

Toxicity: There are data for 3 trophic levels, most sensitive fish NOEC 32 microg/L.

Risk

The risk, PEC/PNEC, calculated from data in the assessment report from a European perspective:

PEC_surfacewater, default or refined (e.g. prevalence, literature) = 0.25 microg/L.

PNEC = Lowest NOEC, 32 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 3.2 microg/L

PEC/PNEC = 0.078 which gives the risk insignificant.

Assessment report on extended indication for Giotrif

Assessment report for Giotrif 25 February 2016, EMA/CHMP/206630/2016.

"The screening for the potential for bioaccumulation/biomagnification as well as the screening for a risk for the terrestrial compartment in the approved ERA for afatinib also revealed no concern."

Fass environmental information

Fass environmental information for Giotrif from Boehringer Ingelheim (downloaded 2024-06-14).

Hazard

Persistence: "Afatinib does not pass the ready degradation test but is degraded in sediment where the total system DT₅₀ ≤ 32d and less than 15% remains as the parent compound at the end of the study. Abiotic degradation through hydrolysis is slow. Considering all data, the phrase “Afatinib is degraded in the environment” is assessed as most relevant."

Bioaccumulation: Log D = 3.68 at 7.
"Bioconcentration factor (BCF_fish):
High dose level: 9.7
Low dose level: 9.2 (OECD 305)."

Toxicity: There are data for 3 trophic levels, most sensitive fish NOEC 32 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2020. PEC/PNEC = 0.000015 which gives the risk insignificant.